What are the potential interactions with fluoxetine (Prozac)?

From the Guidelines

Fluoxetine (Prozac) has several important drug interactions that patients should be aware of, and it is crucial to avoid taking MAO inhibitors within 14 days of Prozac due to the risk of serotonin syndrome, a potentially life-threatening condition, as noted in the study by 1. When considering the potential interactions with fluoxetine, it is essential to prioritize the patient's safety and well-being. The study by 1 highlights the importance of caution when prescribing fluoxetine, especially in relation to other medications that increase serotonin levels, such as other antidepressants, certain pain medications (tramadol), and some supplements (St. John's Wort). Some key points to consider when prescribing fluoxetine include:

• Avoiding the use of MAO inhibitors within 14 days of fluoxetine due to the risk of serotonin syndrome
• Being cautious when prescribing fluoxetine with other medications that increase serotonin levels, such as other antidepressants, certain pain medications, and some supplements
• Monitoring for potential interactions with medications that affect heart rhythm, such as antipsychotics
• Limiting alcohol consumption, as it can worsen side effects
• Informing healthcare providers about all medications, supplements, and herbal products being taken before starting fluoxetine The study by 1 also notes that fluoxetine can increase blood levels of certain medications, such as warfarin, phenytoin, and tricyclic antidepressants, by inhibiting liver enzymes that metabolize these drugs. Additionally, NSAIDs and aspirin may increase bleeding risk when combined with fluoxetine. In terms of dosing, the study by 1 suggests that fluoxetine can be effective in treating premature ejaculation at doses ranging from 5 to 20 mg/day. However, it is essential to weigh the potential benefits against the risks of adverse effects, particularly at higher doses. Overall, when prescribing fluoxetine, it is crucial to prioritize the patient's safety and well-being by being aware of potential interactions and taking steps to minimize risks.

From the FDA Drug Label

phenothiazines and most atypicals), and antiarrhythmics (e.g., propafenone, flecainide, and others) should be approached with caution. Therapy with medications that are predominantly metabolized by the CYP2D6 system and that have a relatively narrow therapeutic index (see list below) should be initiated at the low end of the dose range if a patient is receiving fluoxetine concurrently or has taken it in the previous 5 weeks Thus, his/her dosing requirements resemble those of poor metabolizers. If fluoxetine is added to the treatment regimen of a patient already receiving a drug metabolized by CYP2D6, the need for decreased dose of the original medication should be considered. Drugs with a narrow therapeutic index represent the greatest concern (e.g., flecainide, propafenone, vinblastine, and TCAs). Due to the risk of serious ventricular arrhythmias and sudden death potentially associated with elevated plasma levels of thioridazine, thioridazine should not be administered with fluoxetine or within a minimum of 5 weeks after fluoxetine has been discontinued (see CONTRAINDICATIONS and WARNINGS) CNS active drugs — The risk of using Prozac in combination with other CNS active drugs has not been systematically evaluated. Nonetheless, caution is advised if the concomitant administration of Prozac and such drugs is required In evaluating individual cases, consideration should be given to using lower initial doses of the concomitantly administered drugs, using conservative titration schedules, and monitoring of clinical status (see Accumulation and slow elimination under CLINICAL PHARMACOLOGY) Anticonvulsants — Patients on stable doses of phenytoin and carbamazepine have developed elevated plasma anticonvulsant concentrations and clinical anticonvulsant toxicity following initiation of concomitant fluoxetine treatment. Antipsychotics — Some clinical data suggests a possible pharmacodynamic and/or pharmacokinetic interaction between SSRIs and antipsychotics Elevation of blood levels of haloperidol and clozapine has been observed in patients receiving concomitant fluoxetine. Benzodiazepines — The half–life of concurrently administered diazepam may be prolonged in some patients (see Accumulation and slow elimination under CLINICAL PHARMACOLOGY). Coadministration of alprazolam and fluoxetine has resulted in increased alprazolam plasma concentrations and in further psychomotor performance decrement due to increased alprazolam levels Lithium — There have been reports of both increased and decreased lithium levels when lithium was used concomitantly with fluoxetine. Tryptophan — Five patients receiving Prozac in combination with tryptophan experienced adverse reactions, including agitation, restlessness, and gastrointestinal distress. Monoamine oxidase inhibitors — See CONTRAINDICATIONS Other drugs effective in the treatment of major depressive disorder — In 2 studies, previously stable plasma levels of imipramine and desipramine have increased greater than 2– to 10–fold when fluoxetine has been administered in combination. Serotonergic drugs — Based on the mechanism of action of SNRIs and SSRIs, including Prozac, and the potential for serotonin syndrome, caution is advised when Prozac is coadministered with other drugs that may affect the serotonergic neurotransmitter systems, such as triptans, linezolid (an antibiotic which is a reversible non–selective MAOI), lithium, tramadol, or St John’s Wort (see Serotonin Syndrome under WARNINGS).

The potential interactions with fluoxetine (Prozac) include:

• CNS active drugs: caution is advised when coadministering with other CNS active drugs, and consideration should be given to using lower initial doses and conservative titration schedules.
• Anticonvulsants: may develop elevated plasma anticonvulsant concentrations and clinical anticonvulsant toxicity.
• Antipsychotics: possible pharmacodynamic and/or pharmacokinetic interaction, elevation of blood levels of haloperidol and clozapine.
• Benzodiazepines: may prolong the half-life of concurrently administered diazepam, and increase alprazolam plasma concentrations.
• Lithium: reports of both increased and decreased lithium levels when used concomitantly with fluoxetine.
• Tryptophan: adverse reactions, including agitation, restlessness, and gastrointestinal distress.
• Monoamine oxidase inhibitors: contraindicated due to the risk of serious, sometimes fatal, reactions.
• Serotonergic drugs: caution is advised when coadministering with other drugs that may affect the serotonergic neurotransmitter systems, such as triptans, linezolid, lithium, tramadol, or St John’s Wort, due to the potential for serotonin syndrome.
• Drugs metabolized by CYP2D6: may require decreased dose of the original medication, and plasma concentrations may need to be monitored temporarily when fluoxetine is coadministered or has been recently discontinued 2.
• Pimozide and thioridazine: contraindicated due to the risk of serious ventricular arrhythmias and sudden death 2.

From the Research

Potential Interactions with Fluoxetine (Prozac)

The potential interactions with fluoxetine (Prozac) are a significant concern due to its widespread use and the complexity of its pharmacokinetic and pharmacodynamic properties. Some of the key interactions include:

• Pharmacokinetic interactions: Fluoxetine is metabolized in the liver by the cytochrome P450 (CYP) enzyme system, which can lead to interactions with other medications that are also metabolized by this system 3.
• Pharmacodynamic interactions: Fluoxetine can interact with other medications that affect the serotonin system, such as monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants, and other selective serotonin reuptake inhibitors (SSRIs) 4, 5, 6.
• Serotonin syndrome: The concomitant use of fluoxetine with other serotonergic agents can increase the risk of serotonin syndrome, a potentially life-threatening condition characterized by symptoms such as confusion, fever, shivering, and hyperreflexia 4, 5, 6.
• Interactions with other psychotropics: Fluoxetine can interact with other psychotropics, such as lithium, clozapine, and methadone, which can increase the risk of adverse effects or reduce the efficacy of these medications 4, 6.
• Interactions with non-psychotropic medications: Fluoxetine can also interact with non-psychotropic medications, such as carbamazepine, phenytoin, and oral anticoagulants, which can increase the risk of adverse effects or reduce the efficacy of these medications 4.

Specific Interactions

Some specific interactions with fluoxetine include:

• MAOIs: The concomitant use of fluoxetine with MAOIs can increase the risk of serotonin syndrome and is generally not recommended 4, 5, 6.
• Tricyclic antidepressants: The concomitant use of fluoxetine with tricyclic antidepressants can increase the risk of serotonin syndrome and may require dose adjustments 4, 6.
• Lithium: The concomitant use of fluoxetine with lithium can increase the risk of serotonin syndrome and may require dose adjustments 4, 6.
• Clozapine: The concomitant use of fluoxetine with clozapine can increase the risk of adverse effects, such as seizures and orthosteric hypothermia 6.